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Folic Acid

Folic acid, the synthetic form of folate, is an essential B-vitamin most well known for its role in preventing neural tube defects in infants. It also has a role in supporting general health but may be detrimental in high amounts.

Our evidence-based analysis on folic acid features 175 unique references to scientific papers.

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Summary of Folic Acid

Primary information, health benefits, side effects, usage, and other important details

Folate is the essential vitamin sometimes referred to as Vitamin B9, but more commonly known by its synthetic supplemental form 'folic acid'. Found in low levels across most food products of plant origin and found in enhanced levels in some nation's wheat grain due to fortification, folic acid is a vitamin that has essential roles in the growth of neonates as well as in supporting a process known as methylation in adults.

Folic acid is primarily known as being the 'pregnancy supplement' where women who are planning to conceive children take 400 μg folic acid daily. This is critical in preventing something known as 'neural tube defects' (NTDs) which are caused by insufficient folate provision to the fetus when their neural tube is being formed and the combination of food fortification and supplementation has greatly prevented.

Beyond that, folate and folic acid are used to support methylation in the body. These two supplements, due to eventually forming a molecule known as 5-methyltetrahydrofolate (5-MTHF or L-methylfolate) are involved in indirectly supporting and creating S-Adenosyl Methionine (SAMe) in the body. Due to this, these supplements tend to show quite a bit of similarity to SAMe supplementation and some parallel to supplements involved in the alternate pathway which support SAMe levels (of which supplements like creatine and trimethylglycine (TMG) are implicated in). These parallels are best demonstrated in their effects on depression where they all seem to be implicated in supporting serotonin-based medication (SSRIs usually) as adjuvant with a trend to benefit women more than men.

Despite these benefits, folic acid is unlike other B-vitamins where it does appear to have a potential side-effect when taken in high doses. While taking a very large dose of folic acid several thousand times the RDA will not cause immediate harm it appears that prolonged exposure to levels up to 250% the RDA may be associated with a relative increase in the rates of cancer, particularly colon cancer among the elderly; well demonstrated by acute increases in the rates of colon cancer when both Canada and the US introduced fortification (the rates, of which, have been declining beforehand and ever since). Among the B-vitamins, folate seems to be the one where a balance should be strived in your everyday life and high sources of supplemental folate should be avoided if not intended for other purposes.

Finally, supplements tend to be in one of three forms; folate, folic acid, and L-methylfolate. Of these supplements folic acid is the most common but is thought to be negative when overconsumed. L-methylfolate seems the most promising as many people seem to have genetic mutations in the enzyme which produces L-methylfolate from folate and folic acid, so supplementing the latter two only causes a partial backlog in these people whereas supplementing L-methylfolate may circumvent this genetically disadvantageous rate-limiting step. Furthermore, L-methylfolate seems to be the most promising agent to support SAMe levels as SAMe, as a supplement, is quite expensive and this pathway tends to take on more of the workload than the one creatine and TMG are implicated in.

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How to Take

Recommended dosage, active amounts, other details

The supplement folic acid there are a few options depending on which form you decide to take:

  • When supplementing folate, use up to 400 DFE (400 mcg folate)

  • When supplementing folic acid, use up to 400 DFE (200 mcg is taken on an empty stomach, 240 mcg if taken with a meal)

  • When supplement L-methylfolate, use in the range of 7.5-15mg a day

Supplementing the low doses of folate or folic acid are more than sufficient, in conjunction with a healthy diet, to support bodily levels of all folate metabolites. The higher dose of L-methylfolate is unnecessary for many but for those who suspect or know they have a genetic mutation in the MTHFR enzyme (see MTHFR section) then it would be prudent to supplement L-methylfolate instead of the other two forms since they are rendered less effective.

All the above do not appear to rely on any timing strategies (single v. multiple doses; morning v. night) and are simply taken once a day.

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Human Effect Matrix

Unlocked for Examine members

The Human Effect Matrix summarizes human studies to tell you what effects Folic Acid has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
grade-b Minor Very High See 2 studies
Limited evidence suggests small reduction in depression symptoms
grade-d Minor - See study
One small study found a decrease in a non-standard measure of symptoms of schizophrenia in people with folate deficiency when using methylfolate.

Studies Excluded from Consideration

  • Contained other compounds alongside the folate[1][2][3][4]

  • Study in folate/folic acid combined with B12 against a placebo not containing B12[5]

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Things to Note

Is a Form Of

  • Essential Vitamin or Mineral

Other Functions:

Also Known As

Folate, Vitamin B9, Pteroyl L-glutamic acid

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Click here to see all 175 references.